In a range of psychiatric conditions, notably including depression, eating disorders, and social anxiety disorder, many who suffer have persistent negative beliefs about themselves—for example, that they are inherently flawed or unlovable. Often, these perceptions of the self are rigidly held, even when experience presents the individual with evidence that their perception is incorrect.

Therapies such as cognitive behavioral therapy (CBT) provide a means for therapists to help such individuals overcome their persistently negative self-perceptions via “cognitive restructuring.” CBT teaches them to recognize negative self-perceptions, and to challenge them via a self-questioning process, the answers to which can empower the individual to act on the problem by exiting the repeating loop of negativity.

Little is known about what happens in the brain when CBT or other therapies succeed in helping patients in the task of cognitive reappraisal. Neuroimaging has identified a set of brain regions that support the cognitive reappraisal of negative emotions that are elicited by provocative images or other stimuli. But it cannot be assumed that the same regions are involved in the restructuring of negative self-beliefs, since these likely engage parts of the brain that specifically help individuals form and sustain a view of who they are—a picture of the self.

A team of researchers led by 2020 BBRF Young Investigator Trevor Steward, Ph.D., of the University of Melbourne, Australia, conducted a series of experiments and analyses to learn more about the neurobiological underpinnings of cognitive restructuring.

In a paper appearing in Molecular Psychiatry, they not only described a novel neural signature that comes into play when a person restructures negative self-beliefs; the team also, in the process, was able to propose a new theory about brain mechanisms responsible for enabling people to sustain complex mental representations of the self. The research has potential implications for targeting brain stimulation treatments to help alleviate symptoms of self-impairing negative self-beliefs.

Dr. Steward and colleagues studied results from 42 healthy volunteers who agreed to ultra-high-resolution fMRI brain imaging performed while they engaged in a multi-stage cognitive restructuring task. The task, conducted via a computer program, involved presenting the participants with a screen displaying a negative belief statement (“I am not good at . . . ”). The participants then had a brief interval in which to decide whether to challenge the statement using a self-questioning method similar to the one used in CBT—or, alternatively, to repeat the statement to themselves. This process was repeated a limited number of times, until at the end of the trial the participant had to chose either to cognitively reframe the statement or repeat it again. Each participant went through 16 such trials.

By discovering how healthy individuals reshape negative beliefs about themselves, the team hopes to form a basis for examining the same process in individuals suffering from a range of psychiatric disorders, including binge eating disorder, which was the focus of Dr. Steward’s Young Investigator grant.

The fMRI data was processed with the help of a sophisticated modeling program that enabled the researchers to make sense of complex neural circuit relationships spanning brain regions. The results gave a picture that, in the team’s words, “represents a major shift” from an existing framework for understanding cognition that is centered on the cerebral cortex.

Specifically, the researchers discovered that cognitive restructuring elicited prominent activation of a circuit linking the frontal part of the brain (i.e., the cortex) with the striatum and thalamus. Most notably, the team called attention to the role of a brain area called the mediodorsal thalamus (MD), located deep in the brain. Seldom examined directly by fMRI due to its location and small size, the MD, the team found, acts to synchronize and integrate prefrontal cortex activity with that of other, interacting, brain systems.

An increase in activity in the MD “acts to increase activity in multiple cortical regions during higher-order processes,” the team observed. At the same time, the medial prefrontal cortex (mPFC) was found to have a reciprocal excitatory effect on MD activity. The relationship between these two processes, they said, suggests that “MD pathways may represent a potential focal stimulation target (i.e., target for brain stimulation used to treat) common mental health disorders” in which negative self-beliefs are involved.

Even more broadly, Dr. Steward and colleagues proposed that the “multifaceted role for the MD” that they identified served to increase the “synchrony” between different cortical regions, which may, in turn, underlie the brain’s remarkable ability to “sustain complex mental representations, including those of the self.”